The character of transition states and their interactions with enzymes will be determined for the series of enzmyes which catalyze the transfer of intact methyl group ("methyl transferases"). This information provides the basis for the synthesis of ultrapotent and ultraspecific drugs, which may function as transition state analog or suicide inhibitors of these enzymes which are important in a variety of medically important circumstances. The key techniques for transition state structural determinations in both enzymic and standard reactions are kinetic isotope effects, of the -D, 13C, 18O and sulfur types. These are interpreted by means of quantum mechanical studies of appropriate potential surfaces and vibrational analysis of sets of transition-state model structures. A secondary role is played by the measurement and analysis , for both enzymic and standard reactions, of the enthalpy, entropy, heat capacity and volume of activaton, from which emerge the corresponding quantities for the binding of standard transition state to the enzyme.